Several studies have shown that individuals of African
descent respond less well to interferon-based therapy for chronic
hepatitis C, with a significantly lower proportion of black than white
patients achieving sustained virological response.

As reported in the August 2006 issue of Hepatology, researchers from
Stanford University School of Medicine conducted a study to investigate the
underlying host immune responses associated with interferon treatment
outcomes. The authors collected peripheral blood mononuclear cells from
chronic hepatitis C patients before initiation of interferon therapy; cells
were incubated with or without interferon-alpha for six hours. They then
used a microarray assay to identify whether gene transcription was
stimulated by interferon.

Results

The global induction of interferon-stimulated
genes was significantly greater in sustained virological responders compared
with non-responders.

Interferon-stimulated gene transcription was
also greater in white patients compared with black patients.

Significantly greater global induction of
interferon-stimulated genes was observed in sustained virological responders
compared with nonresponders within the group of white patients.

The level of interferon-induced signal
transducer and activator of transcription (STAT)-1 activation -- a key
component of the JAK-STAT interferon-signaling pathway -- correlated with
the global induction of interferon-stimulated genes.

STAT-1 activation was significantly higher in
white patients than in black patients.

Conclusion

"Both treatment outcome and race are associated with different
transcriptional responses to interferon-alpha," the authors concluded.
"Because this difference is evident in the global induction of
interferon-stimulated genes rather than a selective effect on a subset of
such genes, key factors affecting the outcome of interferon-alpha therapy
are likely to act at the JAK-STAT pathway that controls transcription of
downstream interferon-stimulated genes."